BACKGROUND: The aim of the study was to determine pregnancy-associated plasma protein-A (PAPP-A), which was recently described as a new marker of cardiovascular events, in patients with chronic renal insufficiency/failure and to find out its relationship to renal function and to prominent markers of oxidative stress (advanced oxidation protein products--AOPP) and inflammation (C-reactive protein--CRP). METHODS: The studied group consisted of 36 chronic hemodialysis patients (HD), 10 patients treated with continuous ambulatory peritoneal dialysis (CAPD) and 38 patients with chronic renal insufficiency (CHRI) not yet dialyzed. PAPP-A was measured by Time Resolved Amplified Cryptate Emission technology. Determination of AOPP is based on a spectrophotometric method. RESULTS: PAPP-A levels are statistically significantly elevated in the both groups of dialyzed patients in comparison with healthy subjects (27.0 +/- 16.5 mIU/l in HD and 14.07 +/- 6.73 mIU/l in CAPD vs. 8.22 +/- 2.7 mIU/l in the control group, p < 0.0001 and p < 0.001, respectively, p < 0.05 HD vs. CAPD). The mean serum PAPP-A levels in the CHRI patients not yet dialyzed were not significantly higher in comparison with the control group (9.72 +/-4.44 vs. 8.22 +/- 2.7 mIU/l, n.s.). In the CHRI not dialyzed patients, we found a significant positive correlation between serum creatinine and PAPP-A levels (r = 0.68, p < 0.05). In comparison with controls, AOPP and CRP levels were significantly higher in HD patients [AOPP 155.0 +/- 37.9 micromol/l, p < 0.0001 vs. controls, CRP 10.0 (4.6- 26.9) mg/l (median, interquartile range), p < 0.0001 vs. controls], CAPD patients [AOPP 118.5 +/- 25.8 micromol/l, p < 0.0001 vs. controls, CRP 7.7 (2.0-18.8) mg/l, p < 0.01 vs. controls] and AOPP levels in chronic renal failure patients not yet dialyzed (98.5 +/- 43.24 micromol/l, p < 0.01 vs. controls). The correlations between PAPP-A and AOPP (r = 0.49, p < 0.05) and PAPP-A and CRP (r = 0.48, p < 0.05) serum concentration were statistically significant in HD patients. In CAPD patients, neither a correlation between PAPP-A and AOPP nor a correlation between PAPP-A and CRP were found. CONCLUSION: We can conclude that serum PAPP-A levels sensitively reflect the changes in renal function, depend on dialysis modality, and may represent a novel marker associated with inflammation and oxidative stress in chronic renal failure patients.

Institute of Medical Biochemistry 1st Faculty of Medicine Charles University Prague Czech Republic

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